Bone is the structural material of the body's framework and serves to maintain the necessary bone mass and structure. Bone contains calcium (Ca2+) and plays an important role in maintaining the calcium level in the blood. To this end, the growth of bone is a metabolic balance between the activity of osteoblasts and osteoclasts in the bone remodeling cycle. When the balance between bone absorption and bone formation is disrupted, the amount of bone tissue replaced by osteoblasts fails to match that absorbed by osteoclasts, thus leading to osteoporosis, a common condition causing loss of bone density or bone mass. Osteoblasts are bone forming cells that originate from mesenchymal stem cells (MSCs). Osteoblasts have a very important role in creating and maintaining skeletal architecture. The formation of bone involves a complex series of events that include the proliferation and differentiation of osteoblasts, finally resulting in the mineralization of extracellular matrix. Specific genes are sequentially expressed or repressed during each stage of osteoblast development; for example, histone 4 is a marker for proliferation, alkaline phosphatase (ALP) for differentiation, and osteocalcin for mineralization. In terms of human health, bone formation is a key clinical concern for proper growth of bones in infants and children, prevention of bone mass loss in climacteric women, as well as healing and remodeling of bone fractures in patients. In order to prevent bone loss and increase bone formation, nutritional and pharmacological agents are needed. Therefore, in vitro models of osteoblast primary cell culture have been widely used to find new agents that induce osteoblast differentiation, matrix mineralization, and new bone formation. There are a number of parameters that influence the expression of the osteoblastic phenotype in cell culture.
Bone disease such as osteoporosis is common among middle-aged or elderly women. Examples of therapeutic agents used for osteoporosis include, but is not limited to, bisphosphonate products (alendronate, etidronate), hormone products (raloxifene), vitamin D products, calcitonin products and calcium products. However, bisphosphonate products have problems of low absorption rate and troublesome administration methods and may induce esophagitis. Hormone products require life-time administration and have potential side effects such as breast cancer, uterine cancer, cholelithiasis and thrombosis. Vitamin D products are expensive and not very effective. Calcitonin products also have problems of high cost and difficult administration. Calcium products have less side effects but are limited to prevention rather than treatment. Therefore, there is a need for new osteoporosis therapies.
Herbal therapies have increasingly been considered viable alternative treatments for various diseases. U.S. Pat. No. 5,478,549 relates to a method for orally inducing and enhancing the absorption of calcium into mammalian bone tissue comprising the administration of an effective dose of a flavonol aglycone glycoside in combination with nutritional calcium. U.S. Pat. No. 6,340,703 provides a method for the treatment or prevention of osteoporosis comprising administering to a subject in need of such treatment a therapeutically effective amount of the isoflavono formononetin optionally administered with one or more pharmaceutically acceptable adjuvants, carriers and/or excipients. U.S. Pat. No. 7,122,214 uses Rhizoma Drynariae extract (RDE) as therapeutic agent for osteoporosis. U.S. Pat. No. 7,350,914 provides a pharmaceutical or medicinal preparation comprising a mixture of herbs including Glycine max, Coleus forskohlii, Camellia sinensis, Allium sativum, Withania somnifera, Boerhavia diffusa, and Curcuma longa, or a mixture of the active ingredients that have been extracted from those herbs. U.S. Pat. No. 8,153,167 provides a composition derived from six plant materials: (i) Herba epimedii (Yin Yang Huo) (ii) Fructus Psoraleae (Psoralea coryfolia) (Bu Gu Zhi) (iii) Radix Rehmanniae preparatae (Rehmannia glutinosa) (Shu Di) (iv) Cortex Eucommiae (Du Zhong) (v) Fructus Cnidii (She Chuang Zhi) (vi) Radix Astragali (Astragalus Membranaceus) (Huang Qi); the composition is useful in treating conditions linked to the activity of osteoblasts and/or osteoclasts, such as osteoporosis and other conditions relating to bone mass or menopause, obesity, glucose intolerance, and diabetes. Other traditional Chinese herbal medicines having potential efficacy on bone formation in previous studies include Puerariae radix (Wang, X., Wu, J., Chiba, H., Yamada, K., & Ishimi, Y. (2005). Puerariae radix prevents bone loss in castrated male mice. Metabolism, 54, 1536-1541.), Drynariae rhizome (Jeong, J. C., Lee, J. W., Yoon, C. H., Lee, Y. C., Chung, K. H., Kim, M. G., & Kim, C. H. (2005). Stimulative effects of Drynariae Rhizoma extracts on the proliferation and differentiation of osteoblastic MC3T3-E1 cells. Journal of Ethnopharmacology, 96, 489-495.), and Epimedium pubescens (Hsieh, T. P., Sheu, S. Y., Sun, J. S., Chen, M. H., & Liu, M. H. (2010). Icariin isolated from Epimedium pubescens regulates osteoblasts anabolism through BMP-2, SMAD4, and Cbfa1 expression. Phytomedicine, 17, 414-423).
Uraria crinita (L.) Desv. Ex DC. (Fabaceae) is a traditional edible herb widely distributed throughout India, Thailand, Indonesia, southern China, and Taiwan. It is reported to be effective in repressing stress ulcers. U. crinita shows nitric oxide-scavenging and antioxidant effects in vitro (Luo, C., Liu, A. M., Xing, W. Q., Shi, G., Cao, Y., Pang, J. X., & Qiu, Y. C. (2011). Antioxidant effect of flavonoids from Uraria crinita. Zhongguo Shiyan Fangjixue Zazhi, 17, 198-201.). Its use for the treatment of coldness, swelling, stomachalgia, and ulcers may be due to its anti-inflammatory activities. In Taiwan, people cook it in water and drink it like ginseng tea for its flavor, fragrance, sweetness, and to quench thirst, and so it has been also called “Taiwanese ginseng.” In addition, its roots have been used in Traditional Chinese medicine dietary supplementation for treatment of skeletal dysplasia in children, as well as sport-related, bone twist, sprain and strain injuries (Machida, K., Sakamoto, S., & Kikuchi, M. (2009). Two new neolignan glycosides from leaves of Osmanthus heterophyllus. Journal of Natural Medicines, 63, 227-231).
However, there are no reports showing that U. crinita is associated with bone diseases.